Palladium-catalyzed bisolefination of C-C triple bonds: A facile method for the synthesis of naphthalene derivatives

Article abstract of DOI:10.1021/ja108998d

A highly efficient and mild palladium-mediated bisolefination of C-C triple bonds is described for the first time. With different types of olefin employed, this reaction terminates in diverse fashions. In addition to the merit of using oxygen as the sole

Full text of DOI:10.1021/ja108998d

Published on Web 11/29/2010
Palladium-Catalyzed Bisolefination of C-C Triple Bonds: A Facile Method for
the Synthesis of Naphthalene Derivatives
Chao Feng and Teck-Peng Loh*
DiVision of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang
Technological UniVersity, Singapore 637371
Received October 15, 2010; E-mail: teckpeng@ntu.edu.sg
Table 1. Optimization of Reaction Conditionsa
Abstract: A highly efficient and mild palladium-mediated bisole-
fination of C-C triple bonds is described for the first time. With
different types of olefin employed, this reaction terminates in
diverse fashions. In addition to the merit of using oxygen as the
sole oxidant, this reaction exhibits high reactivities and functional-
ity tolerance simultaneously, thus providing a promising method
for the synthesis of naphthalene derivatives.
entry
catalyst
oxidant
solvent
yield (%)b
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
none
Pd(acac)2
Pd(PPh3)4
Pd(MeCN)2Cl2
PdCl2
PdCl2
PdCl2
Cu(OAc)2/O2
Cu(OAc)2/O2
Cu(OAc)2/O2
AgOAc/air
Cu(OAc)2/air
O2
DMSO
toluene
DMF
DMSO
DMA
15
NR
trace
trace
trace
20
20
64
trace
trace
trace
0c
54
60
70
78
trace
77
75
In the past decades, reactions catalyzed by palladium have found
widespread application in organic synthesis.1 In this regard,
nucleopalladation of alkynes continues to be a hot and fantastic
arena because of its high efficiency in constructing multiple new
chemical bonds, thus leading to various complex structures in one
step. Therefore, much effort has been devoted to this area, utilizing
different kinds of nucleophiles such as halide,2 acetate,3 and amine4
together with aromatic coupounds5 for construction of a wide variety
of desired structures. Gevorgyan,6 Yamamoto,7 and Larock8 have
made great contributions to alkyne-directed transformations. How-
ever, to the best of our knowledge, to date there has been no report
of bisolefination of C-C triple bonds in palladium chemistry.
Toward this end, we envisioned that the use of an alkene as the
initiator for nucleopalladation of an alkyne followed by coupling
with another alkene would allow the concise construction of triene
derivatives.9 If this approach is feasible, it would be an ideal method
for the synthesis of triene derivatives because no prefunctionalized
coupling partners such as organohalides and/or organometallics
would be required, making it environmentally friendly and cost-
effective.10 In connection with our interest in the search for new
coupling reactions for the synthesis of naphthalene derivatives, we
present a palladium-catalyzed sequential intra- and intermolecular
coupling reaction with molecular oxygen as the sole oxidant to
construct naphthalene derivatives with high regioselectivity.
To begin our study, 1-(phenylethynyl)-2-vinylbenzene was first
reacted with butyl acrylate under various conditions, but the reaction
gave intractable mixtures in all cases. Considering that this may
have been due to ꢀ-hydride elimination, we installed a methyl group
at the R-position of the styrene derivative. Fortunately, the reaction
proceeded as expected, albeit in low yield. With this promising
preliminary result in hand, different catalysts, solvents, and oxidants
were screened, and the results are summarized in Table 1. As shown
in Table 1, our attempts to use Pd(OAc)2 as the catalyst were not
successful (entries 1-6). When the catalyst was changed to
Pd(TFA)2 with Cu(OAc)2/air as the oxidant, there was still no
improvement in the yield of the product. Surprisingly, the yield
was dramatically increased to 64% when Cu(OTf)2/air was used
the oxidant (entry 8). After many attempts, it was found that the
reaction proceeded well in DMSO (entries 8-11). As expected,
there was no reaction in the absence of palladium catalyst (entry
DMSO
DMSO
DMSO
toluene
dioxane
DCE
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Cu(OAc)2/air
Cu(OTf)2/air
Cu(OTf)2/air
Cu(OTf)2/air
Cu(OTf)2/air
Cu(OTf)2/air
Cu(OTf)2/air
Cu(OTf)2/air
Cu(OTf)2/air
Cu(OTf)2/air
Ag2O/air
9
10
11
12
13
14
15
16
17
18
19
BQd/air
O2
PdCl2
a Unless otherwise noted, the reactions were carried out at 110 °C
using 1a (0.1 mmol), 2a (0.3 mmol), catalyst (0.005 mmol), oxidant
(0.02 mmol), and DMSO (0.4 mL) for 24 h under air or oxygen
atmosphere. b Isolated yields. c A quantitative amount of 1a was
recovered. d BQ ) 1,4-benzoquinone.
12). With this optimum oxidant system of Cu(OTf)2/air in hand,
various palladium catalysts were screened to ascertain their ef-
ficiency in the reaction (entries 13-16). These results showed that
while many types of palladium catalysts could catalyze this reaction,
the use of palladium chloride as the catalyst gave the best results
(78% yield; entry 16). Further examination of several oxidant
systems using palladium chloride as the catalyst proved that 1,4-
benzoquinone (BQ)/air and molecular oxygen were also suitable
for this reaction (entries 18 and 19), providing yields comparable
to that for the Cu(OTf)2/air system. On the basis of economic
considerations, the optimized reaction conditions were affirmed as
follows: 5 mol % PdCl2 as the catalyst and molecular oxygen as
the oxidant in DMSO at 110 °C for 24 h.
With the optimized reaction conditions in hand, we next
investigated the scope of the reaction using different types of
external olefins. As shown in Table 2, both acrylate and styrene
derivatives reacted efficiently to afford the desired products in good
to excellent yields. It is noteworthy that styrene derivatives with
both electron-donating and electron-withdrawing substituents could
be smoothly transformed into the desired products in good yields
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17710 J. AM. CHEM. SOC. 2010, 132, 17710–17712
10.1021/ja108998d  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Reaction Scopea
Scheme 1. Proposed Mechanism
the alkyne group was smoothly transformed into the desired product
in good yield, which further proved the involvement of a competi-
tive complexation in the reaction with 1n. Moreover, alkyl- and
alkenyl-tethered substrates were also efficiently converted into the
corresponding products in moderate to good yields (3p-r).
Substrate 3s with a methyl group ortho to the alkenyl moiety
resulted in a moderate yield, mainly because of repulsion between
the two adjacent methyl groups. Substrates possessing alkoxy
substituents on the aromatic ring of styrene derivatives could also
be successfully transformed into the corresponding products, albeit
in low yield (3t and 3u). In addition, a halogen atom on the aromatic
ring was inert in this reaction, allowing it to be used for further
transformation (3v). Furthermore, a variety of substituents on the
alkenyl moiety can be used in this reaction. For instance, both tert-
butyl and phenyl groups at the R-position of the styrene derivatives
were transformed into the corresponding products in excellent yields
(3w and 3x). To further demonstrate the practical utility of this
protocol, a gram-scale reaction was carried out using 1x and 2b to
afford the product 3x in 85% yield.12 It is important to note that
this strategy was also applicable to the annulation of R,ꢀ-
disubstituted substrates regardless of the configuration of the double
bond. For example, the reaction of an E/Z mixture of R,ꢀ-
dimethylstyrene derivative 1y proceeded selectively to give the
desired E-configured product 3y in good yield.
a Unless otherwise noted, the reactions were carried out at 110 °C
using 1 (0.1 mmol), 2 (0.3 mmol), PdCl2 (0.005 mmol), and DMSO (0.4
mL) for 24 h under an oxygen atmosphere. The yields in parentheses
are isolated yields.
A proposed mechanism is illustrated in Scheme 1. Initially, PdII
coordinates with the triple bond, forming the π-complex I. This
initial step makes the alkynyl group electron-deficient and instan-
taneously triggers the intramolecular carbopalladation to afford
intermediate II. From intermediate II shown here, we can under-
stand that the R2 substituent is so crucial for this reaction primarily
because of its role in stabilization of the carbocation generated.
Subsequently, deprotonation and external olefin insertion occur to
produce intermediate IV, which, after ꢀ-hydride elimination,
generates the cyclic product as well as Pd0, which can be reoxidized
to the PdII species by molecular oxygen. We believe that the success
of this transformation relies on the dual roles of the palladium
catalyst, namely, its Lewis acidity and late-transition-metal character.
(3c-h). Vinyl cyanide also worked well for this transformation
(3i). Interestingly, when trimethylsilyl-substituted ethylene or vinyl
acetate was used as the terminating coupling reagent, product 3j
was obtained, suggesting the involvement of a ꢀ-heteroatom
elimination process in the reaction.11 Vinyl phenyl sulfone was not
a good coupling partner, as it afforded the target product in low
yield (3k). Intriguingly, when a vinyl ketone was used as the
external coupling partner, reductive products containing an alkyl
chain were obtained (3l and 3m). This result indicated that the final
protonation step of the catalytic cycle proceeded much faster than
ꢀ-hydride elimination in such cases. To further investigate the scope
of the internal enyne, ethyl acrylate was chosen as the intermolecular
coupling partner. Substrate 1n with a methoxy substituent at the
para position of the tethered phenyl group gave the product in low
yield. This might have been due to competition between the alkyne
and methoxy groups to form a complex with palladium. In
comparison, substrate 1o with a methoxy substituent adjacent to
In conclusion, we have demonstrated the first palladium-catalyzed
bisolefination of C-C triple bonds. This transformation is believed
to be an efficient and sustainable process in which molecular oxygen
is the exclusive oxidant with water as the only byproduct generated.
Additionally, this reaction provides a facile method for the synthesis
of naphthalene derivatives that are of tremendous importance in
medicinal chemistry. Further studies to extend the bisolefination
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J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010 17711

C O M M U N I C A T I O N S
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of C-C triple bonds to intermolecular three-component reactions
are in progress.
Acknowledgment. This research was financially supported by
the Nanyang Technological University and the Singapore Ministry
of Education Academic Research Fund Tier 2 (T206B1221,
T207B1220RS).
Supporting Information Available: Additional experimental pro-
cedures along with chromatograms and spectral data. This material is
available free of charge via the Internet at http://pubs.acs.org.
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Supporting Information.
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17712 J. AM. CHEM. SOC. VOL. 132, NO. 50, 2010